Treatment of endogenous disease states, such as hypercholesterolemia, with the polyesters employed in the present invention is known to the art. Relevant patents include: U.S. Pat. No. 3,600,186 issued Aug. 17, 1971 to Mattson, et al., which discloses and claims a low calorie, fat-containing food composition where from about 10% to about 100% of the total fat consists of polyol fatty acid polyesters.
U.S. Pat. No. 3,954,976 issued May 4, 1976 to Mattson, et al., encompasses polyol fatty acid polyesters in 0.1-5 gram unit doses as pharmaceutical compositions for inhibiting the absorption of cholesterol.
U.S. Pat. No. 3,963,699 issued June 15, 1976 to Rizzi, et al., relates to a solvent-free esterification process for preparing the polyol fatty acid polyesters. A sugar, a fatty acid C.sub.1 -C.sub.2 alkyl ester, an alkali metal fatty acid soap and a base catalyst (alkali metal alloys, alkali metal hydrides, alkali metal alkoxides) are heated to form a homogeneous melt; excess fatty acid alkyl ester is added to form the polyol fatty acid polyesters, which are then separated from the mixture. The process allows drug-quality polyol fatty acid polyesters to be manufactured without a solvent-removal step.
U.S. Pat. No. 4,005,195 issued Jan. 25, 1977 to Jandacek describes anti-anal leakage (AAL) agents used in combination with the liquid polyol fatty acid polyesters. The disclosure relates to: (1) compositions of matter comprising polyol fatty acid polyesters+anti-anal leakage compounds; (2) low calorie foods with polyol fatty acid polyesters+AAL compounds: (3) polyol fatty acid polyesters+AAL in unit dose form as pharmaceuticals; and (4) methods for treating hypercholesterolemia by inhibiting absorption of cholesterol without anal leakage by administering compositions per (1).
U.S. Pat. No. 4,005,196 issued Jan. 25, 1977 to Jandacek, et al., encompasses compositions comprising fat-soluble vitamins in combination with polyol fatty acid polyesters and anti-anal leakage agents.
U.S. Pat. No. 4,034,083 issued July 5, 1977 to Mattson discloses polyol fatty acid polyesters plus fat-soluble vitamins.
Treatment of gallstones by administration of chenodeoxycholic acid is taught by L. S. Goodman and A. Gilman, eds. The Pharmacological Basis of Therapeutics, 5th ed. (1975) p. 972 and references there cited.
J. L. Thistle and L. J. Schoenfield, Gastroenterology 61:488 (1971) teach that clofibrate, used in the treatment of hypercholesterolemia, causes bile to become supersaturated with cholesterol.
The Coronary Drug Project Research Group, N. Engl. J. Med. 296:1186 (May 26, 1977) and J. A. Heady, Bull. WHO 48:243 (1973) describe two large clinical trials of clofibrate, and report a significantly increased incidence of gallbladder disease in patients taking clofibrate.
R. N. Redinger and D. M. Grace, Clin. Res. 66:666A (1976) report increased saturation of bile with cholesterol and formation of cholesterol gallstones in monkeys experimentally administered cholestyramine, another drug prescribed in the treatment of hypercholesterolemia.
Cholestyramine is also taught to reduce biliary levels of chenodeoxycholic acid. See P. D. Wood, et al., Metabolism 21:107 (1972).
An incident involving increased biliary cholesterol levels and development of gallstones in a patient receiving colestipol, also used to treat high serum cholesterol levels, has been reported by S. M. Grundy and H. Y. I. Mok, J. Lab. Clin. Med. 80:354 (1977).
E. Garcia-Romero, et al., J. Surg. Res. 24:62 (1978) disclose the in vitro dissolution of a cholesterol gallstone by immersing the gallstone in a solution of 1500 mg. clofibrate in 5 ml. ethanol--clearly unacceptable as a medical treatment.
L. R. Krasno and D. C. Harrison, N. Engl. J. Med. 297:669 (1977) suggest that elevations of cholesterol concentration in the bile caused by clofibrate may be due to an underlying basic defect in cholesterol metabolism.
I. Makino, et al., J. Lipid Res. 19:723 (1978) describes changes in biliary lipid and biliary bile acid composition in patients after administration of ursodeoxycholic acid.
New Scientist, 82:27 (1979) summarizes the status of current research on ursodeoxycholic acid.
The disclosures of the foregoing patents and publications are hereby incorporated herein by reference.